Sun Rui, Chu Jiyan, Li Ping
Department of Rheumatology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Graduate School, Dalian Medical University, Dalian, Liaoning, China.
Front Immunol. 2024 Dec 11;15:1449969. doi: 10.3389/fimmu.2024.1449969. eCollection 2024.
Idiopathic inflammatory myopathies (IIM) are a group of systemic autoimmune diseases characterized by muscle weakness and elevated serum creatine kinase levels. Recent research has highlighted the role of the innate immune system, particularly inflammasomes, in the pathogenesis of IIM. This review focuses on the role of inflammasomes, specifically NLRP3 and AIM2, and their associated proteins in the development of IIM. We discuss the molecular mechanisms of pyroptosis, a programmed cell death pathway that triggers inflammation, and its association with IIM. The NLRP3 inflammasome, in particular, has been implicated in muscle fiber necrosis and the subsequent release of damage-associated molecular patterns (DAMPs), leading to inflammation. We also explore the potential therapeutic implications of targeting the NLRP3 inflammasome with inhibitors such as glyburide and MCC950, which have shown promise in reducing inflammation and improving muscle function in preclinical models. Additionally, we discuss the role of caspases, particularly caspase-1, in the canonical pyroptotic pathway associated with IIM. The understanding of these mechanisms offers new avenues for therapeutic intervention and a better comprehension of IIM pathophysiology.
特发性炎症性肌病（IIM）是一组以肌肉无力和血清肌酸激酶水平升高为特征的全身性自身免疫性疾病。最近的研究突出了固有免疫系统，特别是炎性小体，在IIM发病机制中的作用。本综述重点关注炎性小体，特别是NLRP3和AIM2及其相关蛋白在IIM发展中的作用。我们讨论了细胞焦亡的分子机制，这是一种引发炎症的程序性细胞死亡途径，及其与IIM的关联。特别是NLRP3炎性小体，已被认为与肌纤维坏死以及随后损伤相关分子模式（DAMP）的释放有关，从而导致炎症。我们还探讨了用格列本脲和MCC950等抑制剂靶向NLRP3炎性小体的潜在治疗意义，这些抑制剂在临床前模型中已显示出在减轻炎症和改善肌肉功能方面的前景。此外，我们讨论了半胱天冬酶，特别是半胱天冬酶-1，在与IIM相关的经典细胞焦亡途径中的作用。对这些机制的理解为治疗干预提供了新途径，并有助于更好地理解IIM的病理生理学。
